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- Title
Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice.
- Authors
Waseda Y; Yasui M; Nishizawa Y; Inuzuka K; Takato H; Ichikawa Y; Tagami A; Fujimura M; Nakao S; Waseda, Yuko; Yasui, Masahide; Nishizawa, Yoriko; Inuzuka, Kanako; Takato, Hazuki; Ichikawa, Yukari; Tagami, Atsuro; Fujimura, Masaki; Nakao, Shinji
- Abstract
<bold>Background: </bold>The role of angiotensin II type 2 receptor (AT2) in pulmonary fibrosis is unknown. To evaluate the influence of angiotensin II type 1 receptor (AT1) and AT2 antagonists in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis.<bold>Methods: </bold>We examined effects of the AT1 antagonist (AT1A) olmesartan medoxomil (olmesartan) and the AT2 antagonist (AT2A) PD-123319 on BLM-induced pulmonary fibrosis, which was evaluated by Ashcroft's pathological scoring and hydroxyproline content of lungs. We also analyzed the cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF).<bold>Results: </bold>With olmesartan, the lung fibrosis score and hydroxyproline level were significantly reduced, and lymphocyte and neutrophil counts and tumor necrosis factor (TNF)-alpha levels in BALF were reduced on day 7. On day 14, macrophage and lymphocyte counts in BALF were reduced, accompanied by a reduction in the level of transforming growth factor (TGF)-beta1. With PD-123319, the lung fibrosis score and hydroxyproline level were reduced. On day 7, macrophage, lymphocyte, and neutrophil counts in BALF were reduced, accompanied by reductions in TNF-alpha and monocyte chemoattractant protein (MCP)-1 levels. On day 14, macrophage, lymphocyte, and neutrophil counts in BALF were also reduced, accompanied by a reduction in the level of macrophage inflammatory protein (MIP)-2 level but not TGF-beta1.<bold>Conclusion: </bold>Both AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.
- Publication
Respiratory Research, 2008, Vol 9, p43
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/1465-9921-9-43